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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Hypermutation as an Evolutionary Mechanism for Achromobacter xylosoxidans in Cystic Fibrosis Lung Infection

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DOI

  1. Bacterial persisters in long-term infection: Emergence and fitness in a complex host environment

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Targeting bioenergetics is key to counteracting the drug-tolerant state of biofilm-grown bacteria

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  3. Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis

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  4. miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence

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  1. Omics-based tracking of Pseudomonas aeruginosa persistence in "eradicated" cystic fibrosis patients.

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Bacterial persisters in long-term infection: Emergence and fitness in a complex host environment

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Gene Loss and Acquisition in Lineages of Pseudomonas aeruginosa Evolving in Cystic Fibrosis Patient Airways

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. A new device to prevent contamination of nasal swabs by Staphylococcus aureus in acute rhinosinuitis

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Achromobacter xylosoxidans can cause chronic infections in the lungs of patients with cystic fibrosis (CF) by adapting to the specific environment. The study of longitudinal isolates allows to investigate its within-host evolution to unravel the adaptive mechanisms contributing to successful colonization. In this study, four clinical isolates longitudinally collected from two chronically infected patients underwent whole genome sequencing, de novo assembly and sequence analysis. Phenotypic assays were also performed. The isolates coming from one of the patients (patient A) presented a greater number of genetic variants, diverse integrative and conjugative elements, and different protease secretion. In the first of these isolates (strain A1), we also found a large deletion in the mutS gene, involved in DNA mismatch repair (MMR). In contrast, isolates from patient B showed a lower number of variants, only one integrative and mobilizable element, no phenotypic changes, and no mutations in the MMR system. These results suggest that in the two patients the establishment of a chronic infection was mediated by different adaptive mechanisms. While the strains isolated from patient B showed a longitudinal microevolution, strain A1 can be clearly classified as a hypermutator, confirming the occurrence and importance of this adaptive mechanism in A. xylosoxidans infection.

Original languageEnglish
JournalP L o S Pathogens
Volume9
Issue number2
ISSN2076-0817
DOIs
Publication statusPublished - 21 Jan 2020

ID: 61989489